Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation

Abstract

The recent synthesis of pyrimidine ribonucleoside-2′,3′-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of ribonucleic acid (RNA) at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3′,5′-linked RNA polymers of extant biochemistry has been lacking (previous attempts led only to short oligomers with mixed linkages). Here we show that the 2′-hydroxyl group of oligoribonucleotide-3′-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, which allows rapid and efficient template-directed ligation. The 2′-O-acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers that possess either 2′- or 3′-terminal phosphates is selective for the 2′-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2′,3′-cyclic phosphates to predominantly 3′,5′-linked RNA via partially 2′-O-acetylated RNA. One theory for the abiogenesis of RNA involves ligation of shorter oligomers that are observed after dry-state condensation of mononucleotides. Here, the chemo- and regioselective acetylation of (oligo)nucleotides in water under prebiotically plausible conditions is described. This remarkable selectivity permits the rapid template-directed ligation of oligomers to favour extant 3′,5′-linkages.

Cite this article

Bowler, F., Chan, C., Duffy, C. et al. Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation. Nature Chem 5, 383–389 (2013). https://doi.org/10.1038/nchem.1626

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